Therapeutic irradiation is commonly used in the management of intracranial neoplasia in man and has associated with it a potential for normal tissue damage which may be life threatening. Aggressive treatments incoporating adjuvant drugs or higher tota doses may increase the liklihood of adverse effects of irradiation. The risks associated with currently used time-dose-fractonation schemes or with newer more innovative fractionation protocols are not clearly defined. A suitable animal model characterized by similar morphologic, functional and pathologic changes after irradiation to those observed in man would be helpful in establishing such risk estimates. The overall objective of this proposal is to study the effects of fractionated doses of X-radiation on the normal canine brain. Quatitative computed tomography (QCT) will be used to noninvasively assess the effects of dose fractionation and totla treatment time on the development of radiation induced brain damage. Tissue characterization in terms of density, contrast enhancement dual energy densitometry and contrast kinetics will be evaluated as a function of dose and time to response. The extent of change will be investigated using volumetric analyses of edema/necrosis, leakiness of the blood-brain-barrier, mass effects and enlargement of the lateral ventricles. QCT findings will be correlated with survival and histopathologic observations. Dose response curves for various fractionation schemes and time between fractions will be used to evaluate repair or recovey processes and will be used to define a quantitative relationship between fraction number and treatment time. This relationship ca be used to estimate the risks of developing normal tissue damage when time-dow-fractionation parameters are changed. The unique value of a non-invasive serial QCT study lies in its ability to document and analyse quantitatively the development of radiation changes with multiple independent endpoints at doses below or equal to a lethal dose. The correlation between these endpoints and histopathology provide useful information concerning the pathophysiology of late radiation injury under a variety of treatment conditions. This type of information will be useful in establishing optimal protocols for the treatment of intracranial tumors in man.